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Diagnosis and Treatment of Tuberculosis in Children
The Medical Clinics of North America March, 1942. St. Louis Number
DIAGNOSIS AND TREATMENT .OF TUBERCULOSIS IN CHILDREN· JEAN V. COOKE, M.D.t ALTHOUGH in children, as in adults, the most frequent primary localization of tuberculosis is in the lungs, the usual manifestations in children are so different from the disease in adults that, from a clinical standpoint, there are few similarities. In adults, for example, the diagnosis is often suspected because of abnormalities detected in physical examination of the lungs, while in infancy and childhood, only a very small percentage of cases show any early pulmonary changes which can be found by the usual methods of physical examination. In children of all ages, the presence of easily demonstrable pulmonary signs in tuberculous infection usually indicates a late and extensive lesion; and while in adults a localized area of pulmonary dulness or rales is the common finding in early tuberculosis, in older children, such signs are far more likely to be of nontuberculous origin than due to tuberculosis. Etiology.-The initial tuberculous infection in children in almost every instance is the result of direct contact with an adult who has an open tuberculous lesion, and the primary portal of entry is the lung parenchyma. While it is possible for infection to arise from ingestion of infected milk with a resulting primary intestinal tuberculosis, such a route is now relatively rare in the United States. This is apparently due to the elimination of the infected animals from dairy herds and to the fact that most of the milk used is pasteurized. From a practical standpoint, tuberculosis in children is to be considered a direct contact infection in which the primary focus is in the lung, while all other routes are unusual.
• FJ:om the Department of Pediatrics, Washington University School of Medicine, and the St. Louis Children's Hospital. t Professor of Pediatrics, Washington University School of Medicine; Associate Physician, St. Louis Children's Hospital. 575
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Classification.-The concept that tuberculous disease shows striking differences in its development and manifestations between the first or initial infection, and a later reinfection appears well established. In adults the usual type of phthisis is of the characteristic reinfection variety and at times older children may develop this reinfection or adult type of disease. Such cases, however, are relatively infrequent and in the majority of instances the disease in children is of the first infection type. In such initial infections the most important consideration which influences the character of the lesion produced is the age of the child when the infection is acquired. In infancy the infection tends to be an acute and serious rapidly spreading disease, while in later childhood the tuberculosis which follows the initial infection is usually much less severe and is likely to remain localized. For clinical and descriptive purposes, tuberculosis in children may be classified as: (1) infantile tuberculosis; (2) juvenile infection; (3) adult type, or reinfection tuberculosis. INFANTILE TUBERCULOSIS
Pathogenesis
The characteristic feature of the infantile type is the relatively rapid spread of the disease. This is apparently associated with a lack of resistance to the extension of the infectious process and is quite similar to the manner in which tuberculosis spreads in the guinea pig after experimental inoculation. In this animal there appears to be no mechanism to arrest the continued and relatively rapid extension of tuberculous infection and within a few weeks the disease has produced very extensive lesions. This is also true in most infections ih infants so that the usual picture tends to be that of an acute rapidly progressive disease. This lack of resistance to the spread of first infection persists through infancy but becomes less striking by the middle of the second year. First infections acquired after infancy usually do not exhibit this unrestrained extension in the pulmonary parenchyma, so that in later childhood the body acquires an ability to inhibit the spread of the tuberculosis. This change is apparently not associated with the development of skin sensitivity, since a positive tuberculin skin test is found with the same regularity in children of all ages after infection. In general, the greater severity of almost all acute infections
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during infancy is well established and this may be attributed to the fact that young children as well as young animals form antibodies much less readily than older ones. In tuberculosis the only readily demonstrable antibody is the complement-fixing antibody, and it has been shown! that, in infants with tuberculosis, this antibody cannot be demonstrated during the first year of life while from the second to the sixth year gradually increasing numbers of infected children develop it. It seems probable that this inability to form complement-fixing antibodies may be associated with a lack of power to form other protective antibodies and may, therefore, have some relation to the rapid spread of tuberculosis in infancy. The view has been expressed by many that the severity of the disease in infancy is due to greater liability to more intimate contact with an open case and to consequent heavy or repeated infection. This may be a factor, but it would appear more likely that in tuberculosis, as in other infections, infants lack an ability to resist extension of the first infection because of defective immune body formation. When tubercle bacilli lodge in the pulmonary parenchyma during infancy, a local proliferative lesion begins, and the process develops in one of three ways: 1. The Proliferative Type.-The local focus of proliferation may spread with moderate rapidity until the area becomes large enough to be detected by clinical signs or by x-ray. Tubercle bacilli are soon carried to the hilar and posterior mediastinal nodes in which a spreading proliferation and caseation also occur. 2. The Exudative or Pneumonic Type.-In some cases the primary proliferative area is accompanied by a pneumonic exudate in the surrounding alveoli which spreads and becomes caseous, often with the later formation of unencapsulated cavities. Here also physical signs of pneumonic consolidation occur and can be demonstrated by x-ray, while the lymph nodes share in the developing lesion. 3. The Glandular Type.-In many instances and especially in later infancy the primary proliferative process in the pulmonary parenchyma remains relatively small and does not spread to a degree sufficient to give physical signs, or even to be demonstrable by x-ray. From it, however, the organisms are carried to to the lymph nodes at the hilum and especially to those in the posterior superior mediastinum, and here the tuberculous process develops to a degree which overshadows the lesion in the parenchyma. In many cases this glandular tuberculosis represents the chief or only lesion seen in x-ray (Fig. 100). It is, of course,
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true that in cases of this type which come to necropsy, the original focus in the pulmonary parenchyma is almost always demonstrable after careful search even though the disease is much more extensive in the lymph nodes. It must be understood that the foregoing grouping is made for descriptive purposes and chiefly to serve as a basis for discussion of the clinical types. Practically, although the proliferative or pneumonic or glandular element may dominate the picture in any case, the processes overlap to a considerable degree. In any instance in which the pulmonary disease involves the pleura, a pleurisy results, but this is often not detected clinically. Usually only a small amount of fluid exudes, which gives few clinical signs, and only occasionally in older infants does a massive exudate occur. Such fluid is yellow, shows a predominance of lymphocytes, and soon clots, differing from tuberculous pleural exudates in adults only in having a somewhat higher cell content and more polymorphonuclear elements. Even in later childhood the formation of massive pleural exudates so common in adults, is relatively infrequent. In any type of infantile tuberculosis it is obvious that the lesions must reach a certain size before being demonstrable, and the earliest symptoms of disease may, therefore, be more difficult to recognize. While early development of the infection may follow one of the courses outlined, unless arrested all tend to progress and to terminate in a generalized miliary tuberculosis. The dissemination of the disease always results from the secondary lymph node involvement at the pulmonary hilum. A softened node erodes a small vein with the production of generalized tuberculosis, or, in some instances, the erosion of a bronchus produces an extensive pulmonary dissemination or a rapidly spreading tuberculous pneumonia. In practically all fatal cases of tuberculosis during infancy the disease has become generalized.
Congenital Tuberculosis and Tuberculosis of the Newly Born.-While infection may occur in utero, such instances ap-
pear to be relatively rare, but the newly born are especially susceptible, and rapidly fatal infections acquired in the early days of life are not uncommon. Apparently any baby born of a mother with an open tuberculosis is doomed to an early death unless removed from contact immediately after birth. In three recently observed cases in which the infection was so acquired, the infants lived twenty-five, thirty-two and thirty-
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four days, and all showed very extensive generalized tuberculosis at necropsy. The intradennal tuberculin test was negative in one baby on the twentieth day (two weeks before death) while another showed a positive test on the rwentYfourth day (eight days before death). Clinical Manifestations
The symptoms of infantile tuberculosis in its earlier stages are so few and slight that there is no suspicion of illness. Indeed, it is not uncommon to observe a baby with extensive generalized tuberculosis in whom the symptoms are so mild that the serious character of the disease would never be suspected from them. As the early infantile disease progresses, however, certain features usually become apparent. The most frequent is failure to gain weight, although there is usually little tendency to such gastro-intestinal disturbances as vomiting or diarrhea. Fever is often present, although it may be slight. It often varies from 99° to 102° F. (37.2° to 38.9° C.). Most patients do not appear toxic, while cough and respiratory symptoms are usually absent unless there is some superimposed secondary infection. Eventually, however, with further extension of the lesion, signs of real illness tend to appear, of which fretfulness, irregular fever and often a cough which may assume a "brassy" character, may be prominent. Evidence of pulmonary consolidation may be found in the proliferative or in the pneumonic types with localized rales, while in the glandular type such signs may be absent. The spleen is often palpable. Even in generalized infections few local clinical signs are apparent unless tuberculous meningitis develops. Diagnosis
The diagnosis of infantile tuberculosis is almost entirely dependent upon the use of the tuberculin skin test and x-ray of the chest. The possibility of infection should always be considered when any constitutional symptoms such as fretfulness or fever persist and are unexplained, when an infant fails to gain, or when there is any history of contact with known tuberculosis. Those instances also, in which physical signs of pulmonary consolidation with localized rales in an infant are
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not accompanied by acute pneumonic symptoms, should be suspected. Tuberculin T est.-The most reliable test for clinical use is . the intradermal injection of 0.1 cc. of a 1: 1000 dilution of tuberculin (O.T.) which should be read after forty-eight hours. The patch test, which consists of the application of tuberculin by means-of impregnated adhesive, is only slightly less reliable. The importance of the tuberculin test during infancy is that a properly carried out negative test is quite
Fig. 99.-Infantile Tuberculosis. A fifteen-month-'old baby with pneumonic type of tuberculous pulmonary involvement.
trustworthy in excluding tuberculosis since it is only in very exceptional instances that infected children have negative reactions. On the other hand, a positive tuberculin reaction in itself is usually interpreted to mean only the presence of infection which may be either mild and latent or active disease. During infancy, however, the large majority of babies with positive tuberculin tests have active infections and a positive reaction must therefore be considered of much more .serious import than in an older child. Chest X-ray.-Since a positive tuberculin test indicates
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nothing about the localization of the infection, the frequency of a pulmonary focus makes it necessary to have a chest roentgenogram on all patients with positive reactions. The variation in the picture is considerable, but usually" the lesion revealed is more extensive than is suspected from the clinical signs. It must be remembered also that the x-ray shows only areas which have reached a certain size artd that other early
Fig. IOO.-Infantile Tuberculosis. Mediastinal type of. glandular tuberculosis in a two-year-old child resembling thymic shadow.
developing foci may he present but unrecognizable on the film. A typical film of a fifteen-month-old baby with proliferative-pneumonic type of tuberculosis in the left upper lobe is shown in Fig. 99. The appearance here is not characteristic of tuberculosis and is quite indistinguishable from that seen in an acute pneumonia. The .identification of its tuberculous character must be made by ' the absence of accompanying signs ~nd symptoms of acute pneumonia and by the presence of a positive tuberculin test and possibly other previously mentioned clinical manifeStations suggestive of tuberculous disease. Not all patients show such a clear-cut outline of con-
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COOKE
solidation and at times an irregular patchy shadow may be seen, although almost always the picture suggests an area of pneumonia. . The glandular type of infantile tuberculosis gives a much more characteristic picture. Here the shadow is above the heart and appears to be a widening of the mediastinum as in Fig. 100. This might easily be mistaken for a thymic shadow except that during later infancy, at which time this glandular form is somewhat more common, the thymus is rarely enlarged. The infecteq and visibly enlarged nodes are in the' superior mediastinum. Although those nodes lower at the pulmonary hilum are usually also involved in the infection, they are much less frequently visible in the x-ray during infancy than in later childhood. Such a widened mediastinal shadow in a chest film should arouse the suspicion of tuberculosis which may have been previously unsuspected. Its diagnostic significance has not been emphasized as much as it deserves. Generalized Miliary Tuberculosis.-The certain diagnosis of generalized tubel"culosis can be made only in its later stages when the pumonary foci have become grossly visible and give the characteristic and easily recognized "snowstorm" picture in a chest film. Since no special clinical manifestations accompany the general dissemination of the disease other than may be found in severe localized tuberculosis, the presence of a previously unsuspected miliary tuberculosis may be revealed on x-ray examination. It should also be remembered that even in such films as Figs. 99 and 100, there may be disseminated pulmonary tubercles too small to be seen. The presence of clinical signs of tuberculous meningitis in an infant is almost always an indication of disseminated tuberculosis and in a majority of the fatalities in infantile tuberculosis miliary tuberculosis is found at necropsy. "Healed Milittry Tuberculosis." -Disseminated or miliary tuberculosis represents such an extensive type of infection that recovery is usually believed impossible. There are, however, curious instances both in children and adults in which the x-ray shows many disseminated calcified nodules scattered throughout the lung parenchyma. These are usually found in persons without symptoms and with no history which sug-
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gests such a type of tuberculosis previously. Four children between the ages of eight and thirteen years have been seen in recent years at the St. Louis Children's Hospital with such calcified foci. None had any clinical evidence or history of tuberculous infection and only one had a positive tuberculin skin test. A chest roentgenogram (Fig. 101) of the youngest . child in this group shows the characteristic, scattered, calcified nodules. There is a growing belief that such cases are not
Fig. ,lOl.-"Healed Miliary Tuberculosis." Multiple c:lIcified foci with some hilar thickening in a healthy eight-year-old boy with negative tuberculin reaction.
of tuberculous origin' but are .due to some other cause. One of the suggested explanations, which is supported by considerable evidence, 2 is that they result from a low grade fungus infection with one of the aspergillus group. . Demonstration of Tubercle 'Bacilli in Stomach Washings.It is u~ually so difficult .to obtain sputum in babies that search for tubercle bacilli in gastric contents after fasting is more practical. The washings after lavage with ,about 100 cc. of water are treated with sodium hydroxide to dissolve the
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mucus, centrifuged at high speed, and the sediment stained for acid-fast organisms. Their presence makes the diagnosis absolute, although in most instances in which organisms are demonstrable by this method, the disease has progressed to a fairly advanced stage. Prognosis
The prognosis in infantile tuberculosis is dependent on several factors of which the most important are: (1) the age of the patient, (2) the probability of continued contact with an infected adult, (3) the extent and severity of the lesion, (4) the manner in which the child is reacting to the infection, (5) and the care and attention to proper nursing and nutritional requirements. In earlier infancy the infection is usually more severe and rapidly progressive than later, and it is obvious that those patients who are not removed from contact with the source from which their infection arose will continue to receive organisms. Because the early symptoms of infection are so indefinite, many patients are not seen until the lesions are well advanced, and in such cases the outlook is, of course, serious. Probably one of the most important features in prognosis is the way in which the infant reacts clinically to the infection. If the disease appears to be progressive with continued fever, lack of weight gain, and other evidence of toxicity, the prognosis is grave. On the other hand, when such signs are absent and the patient is free from fever and gaining weight, the outlook for an arrest of the infection is much better. In general, the prognosis of infantile tuberculosis when the lesions have become manifest and easily demonstrable is very serious and the disease tends to progress with moderate rapidity. Not all infants with tuberculous infection progress in this manner and even gross lesions easily demonstrable by x-ray may become arrested and recover. Such an outcome is more frequent in earlier, milder infections. In any individual case the prognosis rests on the factors mentioned- and possibly to differences in individual resistance. Usually no opinion about the outcome is possible until after a varying period of observation.
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Therapy
Probably the first consideration in therapy is the prophy-
laxis of infection. The greatest care should be taken to pro-
tect infants from contact with any person with known tuberculosis, for reasons previously emphasized. This means not only the members of the household but includes nurses and servants. Whenever a tuberculous infection is found in any child, an immediate and careful survey of the familial contacts should be made to determine if possible the source of the disease. It is only by such a search that the individual responsible may be detected and further spread of infection to the patient and possibly to other children prevented. ' After infection has occurred, the treatment is gen~ral and symptomatic. Most important is the nursing, with special attention to nutrition. The diet should be adequate and include all necessary vitamins. Care must be taken to prevent exposure to all infections of the upper respiratory tract, and especially measles and whooping cough. Most young children with evidence of clinical activity can be better treated in a hospital until there is an apparent arrest of active disease. Pathogenesis
JUVENILE TUBERCULOSIS
First tuberculous infections after infancy tend to be of a much milder type than in early life. Mention has been made of the general influence of age on the development of pulmonary tuberculosis 'in children and that in early infancy there is a tendency to nipid spread in the lung parenchyma while in older infants the tuberculous process develops and extends in the bronchial and mediastinal lymph nodes more readily than in the lung itself, In older children the primary focus in the parenchyma has still less propensity for developing the type of proliferative disease common in infantile tuberculosis but usually produces a relatively small and insignificant lesion. The organisms. however, are carried by the lymphatics to the pulmonary hilum and posterior mediastinum which become enlarged from a proliferative tuberculosis. In many such cases followed clinically and by pulmonary x-ray .studies, the absence of demonstrable pulmonary foci is rather remarkable. At necropsy, also, in children who have died from other causes, and in whom these mediastinal glands are found tuberculous, the primary lesion in the lung, if found at
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all, is usually small and well localized. Sometimes only a small calcified nodule remains of this initial "Ghon" lesion. The course of the infection in this juvenile type of tuberculous infection is usually benign, and it remains. well localized in the affected lymph nodes. In this respect there is a much greater resistance to the spread of the disease than during infancy. The development of the lesion in the mediastinal lymph nodes may follow several courses. In the majority of cases there is proliferation of tuberculous tissue with some caseation which remains localized and encapsulated with later fibrosis or calcification. Occasionally there may be softening of a gland and a few tubercle bacilli may reach the blood stream, possibly through the lymphatics, and lodge in various parts of the body. Most of such metastatic lesions probably heal without clinical manifestations and may be accidentally found many years later at necropsy as small fibrous foci. In certain instances, however, some of these organisms may lodge in the growing bony ep~physes with resulting tuberculous .spine or hip, or accidental localization in the nervous system may result in tuberculous meningitis. The glandular lesion also may occasionally become softened, and rupture into a vein with a resultant disseminated tuberculosis in a manner similar to the infantile type, or involve an adjacent portion of the pleura with the production of pleurisy with effusion. Occasionally the nodes may show a massive enlargement with tumorlike extension out into the lung fields (Fig. 105). It is to be emphasized, however, that the characteristic features of juvenile tuberculous first infections are referable to the lymph nodes and not to the pulmonary parenchyma, that most of such infections are relatively benign and localized, and that an extension of the disease may occur in certain children. Clinical Manifestations
The symptoms produced by juvenile tuberculosis are notoriously mild, inconstant and variable. One can only enumerate certain ones which may suggest. the infection. A history . of frequent coughs and colds is common, and the complaint of tiring easily with some disinclination for physical exercise. Appetite may be poor and the weight stationary, although any striking loss of weight is somewhat unusual. Transient periods of slight, unexplained fever may be noted, sometimes with afternoon elevations. A history of known exposure to tuberculosis is inconstant but when present should, of course, excite
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suspicion. Certain symptoms such as cough and night sweats are often present in early tuberculosis in adults, but the error should not be made of considering such symptoms as common manifestations of early tuberculosis in children. While occasionally enlarged tracheobronchial nodes may cause cough in a child, this is of a fairly distinctive "brassy" character, and apparently due to pressure, while a "bronchial cough" in a child is rarely of tuberculous origin. Night sweats also are not especially uncommon in childhood and may be due to a variety of causes. They are of little significance so far as juvenile tuberculosis is concerned. On physical examination, the findings are often equally indefinite. While,severe malnutrition is unusual, most children are on the lower limits of average nutrition for their age and height, and have a mild degree of anemia. The enlarged mediastinal lymph nodes usually give no physical signs, although a very expert observer may sometimes detect slight increase in paravertebral dullness and a positive D'Espine's sign (whispered pectoriloquy extending below the second .dorsal spine). While the presence of phly ctenular conjunctivitis makes the diagnOSis of tuberculosis certain, such children tend to show no more demonstrable evidence of pulmonary disease than those without it, and this is true also of the occasional child with skin tuberculids of the papulonecrotic or lichen scrofulosorum type. The skin tuberculin test is positive and the x-ray shows pulmonary changes which will be mentioned later. In those children in whom the process has spread beyond the usual type of moderate mediastinal proliferation usually present, the chief added symptoms are irregular fever and possibly an increase in asthenia. As a rule, no additional physical signs of pulmonary disease are present except in the occasional instance of pleural effusion. Even in very severe spreading or early generalized infections, the pulmonary physical signs are minimal and usually not detectable by ordinary examination. Lesions from extrapulmonary metastatic foci in such locations as the bones, peritoneum or nervous system usually present obvious clinical signs.
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Diagnosis
As in the infantile type, the use of the tuberculin skin test and chest roentgenogram are the most valuable methods in the diagnosis of juvenile tuberculosis and constitute a most important addition to the rest of the examination. In every case it is usually necessary to review all the data available in order to form a reliable opinion about the extent and severity of the disease. Since there is no single criterion for the degree of . acti,:ity in the infection, a positive tuberculin skin test is a
Fig. 102. Fig. 103. Fig. 102.-Juvenile Tuberculosis. Typical well outlined shadow at right hilum in six-year-old boy. Fig. 103.-Juvenile Tuberculosis. Sharply defined right hilar shadow characteristic of tuberculosis in a ten-year-old child. Tuberculous "mediastinal tumor" also present.
less certain indication of an active infection in older children than during infancy, but it must be remembered that activity cannot always be excluded by the absence of clinical signs of disease. X-ray of the chest in children with the juvenile type of tuberculosis usually. shows a rather characteristic shadow at the right hilum. Although the reason is not well understood, Stills and others have observed that the lymph nodes 011 the right side are involved by the disease more extensively and
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with far greater frequency. than those on the left. This is fortunate for radiologic observation since the left hilum is usually concealed by the heart shadow. The typical picture of juvenile tuberculosis is shown in the roentgenogram of Fig. 102, in which a fairly sharply outlined shadow is seen at the right hilUm just lateral to the heart. The chief characteristics are the location of the shadow just to the right of the heart, often with a rounded, crescentic or triangular shape, and the fairly unifonn densi.ty, although the central portion may be slightly denser than the periphery. While the streaking of increaSed bronchial tree marking may be present in some degree, this is apparently not a part of the tuberculous process and js usually not a prominent feature. . Often the shadow of the enlarged tuberculous nodes is not continuous with the cardiac shadow, but separated from it by a straight or slightly curved" clear, air-containing linear streak of varying width as seen in Fig. 103. In the first x-ray (Fig. 102) is seen the type of shadow to be expected in an early juvenile infection without striking clinical signs,' although the· shadow is often smaller'in size.·The second (Fig. 103), however, shows a much more extensive lesion since in addition :to the, hilar shadow, there is a large tumefaction in the superior mediastinum above the heart. Such a picture in itself suggests a rather alarming degree of activity, and represents one type of spread of juvenile tuberculosis. In neither is there evident any primary focus in the lung parenchyma, arid it is o~y in occasional instances that such an area is apparent in the· film. N ontuberculousinfi1trations of the pulmonary hilum are seen with moderate frequency in children and are usually the result of recurring respiratory infections. Such children often have infected paranasal sinuses and tonsils in which acute infection arises and spreads to the bronchi so that they suffer from subacute recurring bronchitis. The x:..ray picture of such hilar infiltrations has characteristics distinct from those seen in juvenile tuberculosis, and it can usually be distinguished without much difficulty. A typical example of such nontuberculous infiltration is shown in Fig. 104, in which rather course bronchial markings converge at the righthilurn to pro~
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duce a shadow not sharply outlined and with irregular density tending to extend along the bronchi into the lung fields. It lacks the somewhat circumscribed character seen in the tuberculous infection. It is, of course, not possible, or to be expected that one can identify with certainty all juvenile tuberculous infections from an examination of the x-ray alone, and the diagnosis in every case must be made by a review of all available data. It is of interest, however, that from the characteristics out-
Fig. 104. Fig. 105. Fig. 104.-Typical 1lo1ltuberculous pulmonary hilar shadows from re. curring respiratory infections in a six and one-half-year-old child. "Sinus lung." Fig: 10S.-Juvenile Tuberculosis. Extensive spreading active glandular tuberculosis resembling Hodgkin's disease in an eleven-year-old girl. Calcified Ghon tubercle in right lower lobe.
lined, one can after a moderate experience predict with considerable accuracy· from an examination of the chest x-ray alone those children who will have positive tuberculin skin tests. . One type of extension or active spread of juvenile tuberculous infection to the superior mediastinal nodes has been illustrated in Fig. 103. In other instances there may develop a rather massive enlargement of the glands extending out into the lung fields and mediastinum as that shown in Fig. 105.
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Here is seen the site of the O'riginal primary pulmonary infection as a small calcified nodule in the right lower lobe. In other instances a spread to the pulmonary parenchyma may be evidenced by an unexpected triangular shadow extending out from the hilum. In many instances the slightly or moderately enlarged .hilir lymph nodes regress after a varying period, and the only evidence seen in the roentgenogram is an irregular calcification in this area. Such calcification almost always represents an inactive healing lesion. . Therapy
An older child with a positive tuberculin skin test and an x-ray showing some evidence of the hilum infiltration accompanying juvenile tuberculosis, but without clinical signs of disease, is frequently spoken of as having only a "tuberculous infection" which is thought of little importance. Such a child is considered to be in a different cat~gory from children with manifest signs of activity who have "tuberculous disease." While it is true that most children with the juvenile type of tuberculosis tend to recover without serious extension, it must be remembered that those cases in which the disease spreads and becomes manifestly active, have originated in such masked juvenile infections. This indicates the necessity for early recognition of the juvenile type of tuberculosis and for adopting a regimen which will minimize the danger of its spread. It would seem, therefore, that "tuberculous infection" in children should probably be regarded of sufficiently serious potentialities to warrant somewhat more consideration than it is usually given, even though the actual percentage of children who develop a spread of the disease is small. The management of a child in whom the diagnosis of juvenile tuberculosis has been made will depend upon the evidence of activity indicated by a review of the symptoms and the x-ray changes present. Sometimes a period of observation during which temperature readings were recorded is desirable. Symptomfess Cases.-If there are no symptoms, if normal activity does not produce fatigue, temperature remains below 99.5 0 F., the child is alert with good appetite and gaining normally-in weight, and if a positive skin test with some cal-
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cification in the hilar lymph nodes is the only radiologic evidence of an apparently old or latent infection, then no restriction of his normal activities is necessary. He should be examined from time to time to facilitate the early recognition of any unexpected tuberculous activity, while nutrition should be maintained and regular temperate habits should be encouraged. Subclinical Infection.-A child in whom easy fatigability, even moderate malnutrition with anorexia, occasional slight fever, and any symptom suggesting a subacute infection, are present, should occasion more concern. This is especially true when a positive tuberculin test is accompanied by a chest x-ray in which the hilar nodes are sharply visible, moderately enlarged and have the characteristics previously mentioned as often associated with recent infection and subclinical activity. In such instances, somewhat more careful supervision is indicated. As a rule such children need not be kept from school unless the asthenia is striking, since they are not likely to transmit the infection. Exercise and activity should be restricted to that amount which is well tolerated. Respiratory infection should be prevented insofar as possible by adequate clothing and by guarding against chilling from rain and exposure. Regular habits of eating and sleeping are important and a nutritious, high caloric diet is advisable. Sometimes the appetite may be improved by the administration of vitamin B factors. Morning and evening temperatures should be followed, and the development of fever should indicate rest in bed until it subsides. Regular observation of the clinical status and of pulmonary x-ray changes should be continued on such children until the manifestations of even "subclinical" activity disappear. As the child improves, appropriate relaxation of previous restrictions may be allowed with careful check of their effect on the child's progress. Manifest Tuberculous Disease.-Little need be said regarding the management of children in whom tuberculous disease has become manifest, since the principles of therapy are those now generally employed in all active tuberculosis. These include complete bed rest so long as fever is present; an ade-
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quate, well balanced, high caloric diet in which all necessary vitamins are included; suitable exposure to fresh air and judicious use of heliotherapy with carefully graduated exposure to sunlight; the prevention of exposure to acute respiratory infections; and such local or symptomatic treatment as may be indicated in the individual child. Continued clinical observation of the patient's response to the infection together with occasional x-ray check on the progress of the lesion should be carried out until the symptoms disappear and the disease is considered in an inactive stage. This may require a number of months. . With the gradual resumptiot:l of normal &.ctivity the same precautions previously suggested in the ~anagement of initial juvenile infections should be observed. As a rule, drugs play little part in the recovery from tuberculosis, and even the newer sulfonamide products have not been shown to have any definite effect. Drug medication should be used only for specific indications. . Tuberculin in Treatment of Phlyctenular Keratoc.onjunctivitis.-Specific therapy with tuberculin has been unsatisfactory and disappointing except in the treatment of one of the more common manifestations of childhood tuberculosisphlyctenular keratoconjunctivitis. Such "desensitization" with tuberculin is apparently the only form of therapy with any constant beneficial effect on this condition. Subcutaneous injections are given once or twice weekly starting with 0.1 cc. of 1: 1,000,000 dilution of Old Tuberculin. The dose is gradually increased, usually by doubling the preceding dose, until 0,5 cc. of 1: 1000 dilution can be given without signs of local reaction. If such local reaction results from any injection, a reduction of the amount given and more cautious increase is indicated. Clinical improvement is slow and even after recovery there is a tendency for recurrence unless the treatment is supplemented by general hygienic and dietary measures for the relief of the underlying infection. ADULT TYPE OF TUBERCULOSIS IN CHILDHOOD
Children who have previously had an initial infection of the juvenile type of tuberculosis may later become infected again
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from contact with an active case. This reinfection produces a pathologic and clinical picture entirely different from the first infection. The allergic sensitivity to tuberculin which develops soon after the initial infection, and which is manifest by the positive tuberculin skin test, involves all the body tissues and changes their reactivity to the tubercle bacilli and its products. Consequently, when some organisms lodge in the lung of an individual sensitized by a previous infection, a· local proliferative reaction in the pulmonary parenchyma develops. This differs from that seen in the spreading infantile type in being slower in developing and in having a greater tendency to be walled off and to remain circumscribed by the connective tissue proliferation. Some of the infecting organisms are carried to the lymph nodes at the root of the lung, but the glandular manifestations are secondary and overshadowed by those of the process in the parenchyma. This lesion as it develops produces local signs of rales and impaired resonance together with constitutional symptoms of fever and asthenia. The clinical and pathologic picture in children with the reinfection type of tuberculosis as well as the treatment is identical with phthisis in adults. It is essentially a disease of later childhood and only occasionally encountered in younger children. It is believed that in some instances such reinfection tuberculosis may result from an autogenous spread from an activated initial lesion rather than from an outside source. The extent of the pulmonary involvement as shown in the x-ray i~ often much greater than anticipated from the physical SIgns. BIB LIOGRAPHY
1. Cooke, ]. V.: Complement Fixation for Tuberculosis in Children. Am.]. Dis. Child., 21: 78, 1921. 2. Sayers, R. R. and Meriwether, 1':. V.: Miliary Lung Disease Due to Unknown Cause. Am. ]. Roentgenol., 27: 337, 1932. 3. Still, G. F.: Common Disorders and Diseases of Childhood. Ed. 5. Oxford University Press, London, 1927, p. 486.
DIAGNOSIS AND TREATMENT .OF TUBERCULOSIS IN CHILDREN· JEAN V. COOKE, M.D.t ALTHOUGH in children, as in adults, the most frequent primary localization of tuberculosis is in the lungs, the usual manifestations in children are so different from the disease in adults that, from a clinical standpoint, there are few similarities. In adults, for example, the diagnosis is often suspected because of abnormalities detected in physical examination of the lungs, while in infancy and childhood, only a very small percentage of cases show any early pulmonary changes which can be found by the usual methods of physical examination. In children of all ages, the presence of easily demonstrable pulmonary signs in tuberculous infection usually indicates a late and extensive lesion; and while in adults a localized area of pulmonary dulness or rales is the common finding in early tuberculosis, in older children, such signs are far more likely to be of nontuberculous origin than due to tuberculosis. Etiology.-The initial tuberculous infection in children in almost every instance is the result of direct contact with an adult who has an open tuberculous lesion, and the primary portal of entry is the lung parenchyma. While it is possible for infection to arise from ingestion of infected milk with a resulting primary intestinal tuberculosis, such a route is now relatively rare in the United States. This is apparently due to the elimination of the infected animals from dairy herds and to the fact that most of the milk used is pasteurized. From a practical standpoint, tuberculosis in children is to be considered a direct contact infection in which the primary focus is in the lung, while all other routes are unusual.
• FJ:om the Department of Pediatrics, Washington University School of Medicine, and the St. Louis Children's Hospital. t Professor of Pediatrics, Washington University School of Medicine; Associate Physician, St. Louis Children's Hospital. 575
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Classification.-The concept that tuberculous disease shows striking differences in its development and manifestations between the first or initial infection, and a later reinfection appears well established. In adults the usual type of phthisis is of the characteristic reinfection variety and at times older children may develop this reinfection or adult type of disease. Such cases, however, are relatively infrequent and in the majority of instances the disease in children is of the first infection type. In such initial infections the most important consideration which influences the character of the lesion produced is the age of the child when the infection is acquired. In infancy the infection tends to be an acute and serious rapidly spreading disease, while in later childhood the tuberculosis which follows the initial infection is usually much less severe and is likely to remain localized. For clinical and descriptive purposes, tuberculosis in children may be classified as: (1) infantile tuberculosis; (2) juvenile infection; (3) adult type, or reinfection tuberculosis. INFANTILE TUBERCULOSIS
Pathogenesis
The characteristic feature of the infantile type is the relatively rapid spread of the disease. This is apparently associated with a lack of resistance to the extension of the infectious process and is quite similar to the manner in which tuberculosis spreads in the guinea pig after experimental inoculation. In this animal there appears to be no mechanism to arrest the continued and relatively rapid extension of tuberculous infection and within a few weeks the disease has produced very extensive lesions. This is also true in most infections ih infants so that the usual picture tends to be that of an acute rapidly progressive disease. This lack of resistance to the spread of first infection persists through infancy but becomes less striking by the middle of the second year. First infections acquired after infancy usually do not exhibit this unrestrained extension in the pulmonary parenchyma, so that in later childhood the body acquires an ability to inhibit the spread of the tuberculosis. This change is apparently not associated with the development of skin sensitivity, since a positive tuberculin skin test is found with the same regularity in children of all ages after infection. In general, the greater severity of almost all acute infections
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during infancy is well established and this may be attributed to the fact that young children as well as young animals form antibodies much less readily than older ones. In tuberculosis the only readily demonstrable antibody is the complement-fixing antibody, and it has been shown! that, in infants with tuberculosis, this antibody cannot be demonstrated during the first year of life while from the second to the sixth year gradually increasing numbers of infected children develop it. It seems probable that this inability to form complement-fixing antibodies may be associated with a lack of power to form other protective antibodies and may, therefore, have some relation to the rapid spread of tuberculosis in infancy. The view has been expressed by many that the severity of the disease in infancy is due to greater liability to more intimate contact with an open case and to consequent heavy or repeated infection. This may be a factor, but it would appear more likely that in tuberculosis, as in other infections, infants lack an ability to resist extension of the first infection because of defective immune body formation. When tubercle bacilli lodge in the pulmonary parenchyma during infancy, a local proliferative lesion begins, and the process develops in one of three ways: 1. The Proliferative Type.-The local focus of proliferation may spread with moderate rapidity until the area becomes large enough to be detected by clinical signs or by x-ray. Tubercle bacilli are soon carried to the hilar and posterior mediastinal nodes in which a spreading proliferation and caseation also occur. 2. The Exudative or Pneumonic Type.-In some cases the primary proliferative area is accompanied by a pneumonic exudate in the surrounding alveoli which spreads and becomes caseous, often with the later formation of unencapsulated cavities. Here also physical signs of pneumonic consolidation occur and can be demonstrated by x-ray, while the lymph nodes share in the developing lesion. 3. The Glandular Type.-In many instances and especially in later infancy the primary proliferative process in the pulmonary parenchyma remains relatively small and does not spread to a degree sufficient to give physical signs, or even to be demonstrable by x-ray. From it, however, the organisms are carried to to the lymph nodes at the hilum and especially to those in the posterior superior mediastinum, and here the tuberculous process develops to a degree which overshadows the lesion in the parenchyma. In many cases this glandular tuberculosis represents the chief or only lesion seen in x-ray (Fig. 100). It is, of course,
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true that in cases of this type which come to necropsy, the original focus in the pulmonary parenchyma is almost always demonstrable after careful search even though the disease is much more extensive in the lymph nodes. It must be understood that the foregoing grouping is made for descriptive purposes and chiefly to serve as a basis for discussion of the clinical types. Practically, although the proliferative or pneumonic or glandular element may dominate the picture in any case, the processes overlap to a considerable degree. In any instance in which the pulmonary disease involves the pleura, a pleurisy results, but this is often not detected clinically. Usually only a small amount of fluid exudes, which gives few clinical signs, and only occasionally in older infants does a massive exudate occur. Such fluid is yellow, shows a predominance of lymphocytes, and soon clots, differing from tuberculous pleural exudates in adults only in having a somewhat higher cell content and more polymorphonuclear elements. Even in later childhood the formation of massive pleural exudates so common in adults, is relatively infrequent. In any type of infantile tuberculosis it is obvious that the lesions must reach a certain size before being demonstrable, and the earliest symptoms of disease may, therefore, be more difficult to recognize. While early development of the infection may follow one of the courses outlined, unless arrested all tend to progress and to terminate in a generalized miliary tuberculosis. The dissemination of the disease always results from the secondary lymph node involvement at the pulmonary hilum. A softened node erodes a small vein with the production of generalized tuberculosis, or, in some instances, the erosion of a bronchus produces an extensive pulmonary dissemination or a rapidly spreading tuberculous pneumonia. In practically all fatal cases of tuberculosis during infancy the disease has become generalized.
Congenital Tuberculosis and Tuberculosis of the Newly Born.-While infection may occur in utero, such instances ap-
pear to be relatively rare, but the newly born are especially susceptible, and rapidly fatal infections acquired in the early days of life are not uncommon. Apparently any baby born of a mother with an open tuberculosis is doomed to an early death unless removed from contact immediately after birth. In three recently observed cases in which the infection was so acquired, the infants lived twenty-five, thirty-two and thirty-
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four days, and all showed very extensive generalized tuberculosis at necropsy. The intradennal tuberculin test was negative in one baby on the twentieth day (two weeks before death) while another showed a positive test on the rwentYfourth day (eight days before death). Clinical Manifestations
The symptoms of infantile tuberculosis in its earlier stages are so few and slight that there is no suspicion of illness. Indeed, it is not uncommon to observe a baby with extensive generalized tuberculosis in whom the symptoms are so mild that the serious character of the disease would never be suspected from them. As the early infantile disease progresses, however, certain features usually become apparent. The most frequent is failure to gain weight, although there is usually little tendency to such gastro-intestinal disturbances as vomiting or diarrhea. Fever is often present, although it may be slight. It often varies from 99° to 102° F. (37.2° to 38.9° C.). Most patients do not appear toxic, while cough and respiratory symptoms are usually absent unless there is some superimposed secondary infection. Eventually, however, with further extension of the lesion, signs of real illness tend to appear, of which fretfulness, irregular fever and often a cough which may assume a "brassy" character, may be prominent. Evidence of pulmonary consolidation may be found in the proliferative or in the pneumonic types with localized rales, while in the glandular type such signs may be absent. The spleen is often palpable. Even in generalized infections few local clinical signs are apparent unless tuberculous meningitis develops. Diagnosis
The diagnosis of infantile tuberculosis is almost entirely dependent upon the use of the tuberculin skin test and x-ray of the chest. The possibility of infection should always be considered when any constitutional symptoms such as fretfulness or fever persist and are unexplained, when an infant fails to gain, or when there is any history of contact with known tuberculosis. Those instances also, in which physical signs of pulmonary consolidation with localized rales in an infant are
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not accompanied by acute pneumonic symptoms, should be suspected. Tuberculin T est.-The most reliable test for clinical use is . the intradermal injection of 0.1 cc. of a 1: 1000 dilution of tuberculin (O.T.) which should be read after forty-eight hours. The patch test, which consists of the application of tuberculin by means-of impregnated adhesive, is only slightly less reliable. The importance of the tuberculin test during infancy is that a properly carried out negative test is quite
Fig. 99.-Infantile Tuberculosis. A fifteen-month-'old baby with pneumonic type of tuberculous pulmonary involvement.
trustworthy in excluding tuberculosis since it is only in very exceptional instances that infected children have negative reactions. On the other hand, a positive tuberculin reaction in itself is usually interpreted to mean only the presence of infection which may be either mild and latent or active disease. During infancy, however, the large majority of babies with positive tuberculin tests have active infections and a positive reaction must therefore be considered of much more .serious import than in an older child. Chest X-ray.-Since a positive tuberculin test indicates
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nothing about the localization of the infection, the frequency of a pulmonary focus makes it necessary to have a chest roentgenogram on all patients with positive reactions. The variation in the picture is considerable, but usually" the lesion revealed is more extensive than is suspected from the clinical signs. It must be remembered also that the x-ray shows only areas which have reached a certain size artd that other early
Fig. IOO.-Infantile Tuberculosis. Mediastinal type of. glandular tuberculosis in a two-year-old child resembling thymic shadow.
developing foci may he present but unrecognizable on the film. A typical film of a fifteen-month-old baby with proliferative-pneumonic type of tuberculosis in the left upper lobe is shown in Fig. 99. The appearance here is not characteristic of tuberculosis and is quite indistinguishable from that seen in an acute pneumonia. The .identification of its tuberculous character must be made by ' the absence of accompanying signs ~nd symptoms of acute pneumonia and by the presence of a positive tuberculin test and possibly other previously mentioned clinical manifeStations suggestive of tuberculous disease. Not all patients show such a clear-cut outline of con-
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COOKE
solidation and at times an irregular patchy shadow may be seen, although almost always the picture suggests an area of pneumonia. . The glandular type of infantile tuberculosis gives a much more characteristic picture. Here the shadow is above the heart and appears to be a widening of the mediastinum as in Fig. 100. This might easily be mistaken for a thymic shadow except that during later infancy, at which time this glandular form is somewhat more common, the thymus is rarely enlarged. The infecteq and visibly enlarged nodes are in the' superior mediastinum. Although those nodes lower at the pulmonary hilum are usually also involved in the infection, they are much less frequently visible in the x-ray during infancy than in later childhood. Such a widened mediastinal shadow in a chest film should arouse the suspicion of tuberculosis which may have been previously unsuspected. Its diagnostic significance has not been emphasized as much as it deserves. Generalized Miliary Tuberculosis.-The certain diagnosis of generalized tubel"culosis can be made only in its later stages when the pumonary foci have become grossly visible and give the characteristic and easily recognized "snowstorm" picture in a chest film. Since no special clinical manifestations accompany the general dissemination of the disease other than may be found in severe localized tuberculosis, the presence of a previously unsuspected miliary tuberculosis may be revealed on x-ray examination. It should also be remembered that even in such films as Figs. 99 and 100, there may be disseminated pulmonary tubercles too small to be seen. The presence of clinical signs of tuberculous meningitis in an infant is almost always an indication of disseminated tuberculosis and in a majority of the fatalities in infantile tuberculosis miliary tuberculosis is found at necropsy. "Healed Milittry Tuberculosis." -Disseminated or miliary tuberculosis represents such an extensive type of infection that recovery is usually believed impossible. There are, however, curious instances both in children and adults in which the x-ray shows many disseminated calcified nodules scattered throughout the lung parenchyma. These are usually found in persons without symptoms and with no history which sug-
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gests such a type of tuberculosis previously. Four children between the ages of eight and thirteen years have been seen in recent years at the St. Louis Children's Hospital with such calcified foci. None had any clinical evidence or history of tuberculous infection and only one had a positive tuberculin skin test. A chest roentgenogram (Fig. 101) of the youngest . child in this group shows the characteristic, scattered, calcified nodules. There is a growing belief that such cases are not
Fig. ,lOl.-"Healed Miliary Tuberculosis." Multiple c:lIcified foci with some hilar thickening in a healthy eight-year-old boy with negative tuberculin reaction.
of tuberculous origin' but are .due to some other cause. One of the suggested explanations, which is supported by considerable evidence, 2 is that they result from a low grade fungus infection with one of the aspergillus group. . Demonstration of Tubercle 'Bacilli in Stomach Washings.It is u~ually so difficult .to obtain sputum in babies that search for tubercle bacilli in gastric contents after fasting is more practical. The washings after lavage with ,about 100 cc. of water are treated with sodium hydroxide to dissolve the
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mucus, centrifuged at high speed, and the sediment stained for acid-fast organisms. Their presence makes the diagnosis absolute, although in most instances in which organisms are demonstrable by this method, the disease has progressed to a fairly advanced stage. Prognosis
The prognosis in infantile tuberculosis is dependent on several factors of which the most important are: (1) the age of the patient, (2) the probability of continued contact with an infected adult, (3) the extent and severity of the lesion, (4) the manner in which the child is reacting to the infection, (5) and the care and attention to proper nursing and nutritional requirements. In earlier infancy the infection is usually more severe and rapidly progressive than later, and it is obvious that those patients who are not removed from contact with the source from which their infection arose will continue to receive organisms. Because the early symptoms of infection are so indefinite, many patients are not seen until the lesions are well advanced, and in such cases the outlook is, of course, serious. Probably one of the most important features in prognosis is the way in which the infant reacts clinically to the infection. If the disease appears to be progressive with continued fever, lack of weight gain, and other evidence of toxicity, the prognosis is grave. On the other hand, when such signs are absent and the patient is free from fever and gaining weight, the outlook for an arrest of the infection is much better. In general, the prognosis of infantile tuberculosis when the lesions have become manifest and easily demonstrable is very serious and the disease tends to progress with moderate rapidity. Not all infants with tuberculous infection progress in this manner and even gross lesions easily demonstrable by x-ray may become arrested and recover. Such an outcome is more frequent in earlier, milder infections. In any individual case the prognosis rests on the factors mentioned- and possibly to differences in individual resistance. Usually no opinion about the outcome is possible until after a varying period of observation.
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Therapy
Probably the first consideration in therapy is the prophy-
laxis of infection. The greatest care should be taken to pro-
tect infants from contact with any person with known tuberculosis, for reasons previously emphasized. This means not only the members of the household but includes nurses and servants. Whenever a tuberculous infection is found in any child, an immediate and careful survey of the familial contacts should be made to determine if possible the source of the disease. It is only by such a search that the individual responsible may be detected and further spread of infection to the patient and possibly to other children prevented. ' After infection has occurred, the treatment is gen~ral and symptomatic. Most important is the nursing, with special attention to nutrition. The diet should be adequate and include all necessary vitamins. Care must be taken to prevent exposure to all infections of the upper respiratory tract, and especially measles and whooping cough. Most young children with evidence of clinical activity can be better treated in a hospital until there is an apparent arrest of active disease. Pathogenesis
JUVENILE TUBERCULOSIS
First tuberculous infections after infancy tend to be of a much milder type than in early life. Mention has been made of the general influence of age on the development of pulmonary tuberculosis 'in children and that in early infancy there is a tendency to nipid spread in the lung parenchyma while in older infants the tuberculous process develops and extends in the bronchial and mediastinal lymph nodes more readily than in the lung itself, In older children the primary focus in the parenchyma has still less propensity for developing the type of proliferative disease common in infantile tuberculosis but usually produces a relatively small and insignificant lesion. The organisms. however, are carried by the lymphatics to the pulmonary hilum and posterior mediastinum which become enlarged from a proliferative tuberculosis. In many such cases followed clinically and by pulmonary x-ray .studies, the absence of demonstrable pulmonary foci is rather remarkable. At necropsy, also, in children who have died from other causes, and in whom these mediastinal glands are found tuberculous, the primary lesion in the lung, if found at
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all, is usually small and well localized. Sometimes only a small calcified nodule remains of this initial "Ghon" lesion. The course of the infection in this juvenile type of tuberculous infection is usually benign, and it remains. well localized in the affected lymph nodes. In this respect there is a much greater resistance to the spread of the disease than during infancy. The development of the lesion in the mediastinal lymph nodes may follow several courses. In the majority of cases there is proliferation of tuberculous tissue with some caseation which remains localized and encapsulated with later fibrosis or calcification. Occasionally there may be softening of a gland and a few tubercle bacilli may reach the blood stream, possibly through the lymphatics, and lodge in various parts of the body. Most of such metastatic lesions probably heal without clinical manifestations and may be accidentally found many years later at necropsy as small fibrous foci. In certain instances, however, some of these organisms may lodge in the growing bony ep~physes with resulting tuberculous .spine or hip, or accidental localization in the nervous system may result in tuberculous meningitis. The glandular lesion also may occasionally become softened, and rupture into a vein with a resultant disseminated tuberculosis in a manner similar to the infantile type, or involve an adjacent portion of the pleura with the production of pleurisy with effusion. Occasionally the nodes may show a massive enlargement with tumorlike extension out into the lung fields (Fig. 105). It is to be emphasized, however, that the characteristic features of juvenile tuberculous first infections are referable to the lymph nodes and not to the pulmonary parenchyma, that most of such infections are relatively benign and localized, and that an extension of the disease may occur in certain children. Clinical Manifestations
The symptoms produced by juvenile tuberculosis are notoriously mild, inconstant and variable. One can only enumerate certain ones which may suggest. the infection. A history . of frequent coughs and colds is common, and the complaint of tiring easily with some disinclination for physical exercise. Appetite may be poor and the weight stationary, although any striking loss of weight is somewhat unusual. Transient periods of slight, unexplained fever may be noted, sometimes with afternoon elevations. A history of known exposure to tuberculosis is inconstant but when present should, of course, excite
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suspicion. Certain symptoms such as cough and night sweats are often present in early tuberculosis in adults, but the error should not be made of considering such symptoms as common manifestations of early tuberculosis in children. While occasionally enlarged tracheobronchial nodes may cause cough in a child, this is of a fairly distinctive "brassy" character, and apparently due to pressure, while a "bronchial cough" in a child is rarely of tuberculous origin. Night sweats also are not especially uncommon in childhood and may be due to a variety of causes. They are of little significance so far as juvenile tuberculosis is concerned. On physical examination, the findings are often equally indefinite. While,severe malnutrition is unusual, most children are on the lower limits of average nutrition for their age and height, and have a mild degree of anemia. The enlarged mediastinal lymph nodes usually give no physical signs, although a very expert observer may sometimes detect slight increase in paravertebral dullness and a positive D'Espine's sign (whispered pectoriloquy extending below the second .dorsal spine). While the presence of phly ctenular conjunctivitis makes the diagnOSis of tuberculosis certain, such children tend to show no more demonstrable evidence of pulmonary disease than those without it, and this is true also of the occasional child with skin tuberculids of the papulonecrotic or lichen scrofulosorum type. The skin tuberculin test is positive and the x-ray shows pulmonary changes which will be mentioned later. In those children in whom the process has spread beyond the usual type of moderate mediastinal proliferation usually present, the chief added symptoms are irregular fever and possibly an increase in asthenia. As a rule, no additional physical signs of pulmonary disease are present except in the occasional instance of pleural effusion. Even in very severe spreading or early generalized infections, the pulmonary physical signs are minimal and usually not detectable by ordinary examination. Lesions from extrapulmonary metastatic foci in such locations as the bones, peritoneum or nervous system usually present obvious clinical signs.
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Diagnosis
As in the infantile type, the use of the tuberculin skin test and chest roentgenogram are the most valuable methods in the diagnosis of juvenile tuberculosis and constitute a most important addition to the rest of the examination. In every case it is usually necessary to review all the data available in order to form a reliable opinion about the extent and severity of the disease. Since there is no single criterion for the degree of . acti,:ity in the infection, a positive tuberculin skin test is a
Fig. 102. Fig. 103. Fig. 102.-Juvenile Tuberculosis. Typical well outlined shadow at right hilum in six-year-old boy. Fig. 103.-Juvenile Tuberculosis. Sharply defined right hilar shadow characteristic of tuberculosis in a ten-year-old child. Tuberculous "mediastinal tumor" also present.
less certain indication of an active infection in older children than during infancy, but it must be remembered that activity cannot always be excluded by the absence of clinical signs of disease. X-ray of the chest in children with the juvenile type of tuberculosis usually. shows a rather characteristic shadow at the right hilum. Although the reason is not well understood, Stills and others have observed that the lymph nodes 011 the right side are involved by the disease more extensively and
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with far greater frequency. than those on the left. This is fortunate for radiologic observation since the left hilum is usually concealed by the heart shadow. The typical picture of juvenile tuberculosis is shown in the roentgenogram of Fig. 102, in which a fairly sharply outlined shadow is seen at the right hilUm just lateral to the heart. The chief characteristics are the location of the shadow just to the right of the heart, often with a rounded, crescentic or triangular shape, and the fairly unifonn densi.ty, although the central portion may be slightly denser than the periphery. While the streaking of increaSed bronchial tree marking may be present in some degree, this is apparently not a part of the tuberculous process and js usually not a prominent feature. . Often the shadow of the enlarged tuberculous nodes is not continuous with the cardiac shadow, but separated from it by a straight or slightly curved" clear, air-containing linear streak of varying width as seen in Fig. 103. In the first x-ray (Fig. 102) is seen the type of shadow to be expected in an early juvenile infection without striking clinical signs,' although the· shadow is often smaller'in size.·The second (Fig. 103), however, shows a much more extensive lesion since in addition :to the, hilar shadow, there is a large tumefaction in the superior mediastinum above the heart. Such a picture in itself suggests a rather alarming degree of activity, and represents one type of spread of juvenile tuberculosis. In neither is there evident any primary focus in the lung parenchyma, arid it is o~y in occasional instances that such an area is apparent in the· film. N ontuberculousinfi1trations of the pulmonary hilum are seen with moderate frequency in children and are usually the result of recurring respiratory infections. Such children often have infected paranasal sinuses and tonsils in which acute infection arises and spreads to the bronchi so that they suffer from subacute recurring bronchitis. The x:..ray picture of such hilar infiltrations has characteristics distinct from those seen in juvenile tuberculosis, and it can usually be distinguished without much difficulty. A typical example of such nontuberculous infiltration is shown in Fig. 104, in which rather course bronchial markings converge at the righthilurn to pro~
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duce a shadow not sharply outlined and with irregular density tending to extend along the bronchi into the lung fields. It lacks the somewhat circumscribed character seen in the tuberculous infection. It is, of course, not possible, or to be expected that one can identify with certainty all juvenile tuberculous infections from an examination of the x-ray alone, and the diagnosis in every case must be made by a review of all available data. It is of interest, however, that from the characteristics out-
Fig. 104. Fig. 105. Fig. 104.-Typical 1lo1ltuberculous pulmonary hilar shadows from re. curring respiratory infections in a six and one-half-year-old child. "Sinus lung." Fig: 10S.-Juvenile Tuberculosis. Extensive spreading active glandular tuberculosis resembling Hodgkin's disease in an eleven-year-old girl. Calcified Ghon tubercle in right lower lobe.
lined, one can after a moderate experience predict with considerable accuracy· from an examination of the chest x-ray alone those children who will have positive tuberculin skin tests. . One type of extension or active spread of juvenile tuberculous infection to the superior mediastinal nodes has been illustrated in Fig. 103. In other instances there may develop a rather massive enlargement of the glands extending out into the lung fields and mediastinum as that shown in Fig. 105.
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Here is seen the site of the O'riginal primary pulmonary infection as a small calcified nodule in the right lower lobe. In other instances a spread to the pulmonary parenchyma may be evidenced by an unexpected triangular shadow extending out from the hilum. In many instances the slightly or moderately enlarged .hilir lymph nodes regress after a varying period, and the only evidence seen in the roentgenogram is an irregular calcification in this area. Such calcification almost always represents an inactive healing lesion. . Therapy
An older child with a positive tuberculin skin test and an x-ray showing some evidence of the hilum infiltration accompanying juvenile tuberculosis, but without clinical signs of disease, is frequently spoken of as having only a "tuberculous infection" which is thought of little importance. Such a child is considered to be in a different cat~gory from children with manifest signs of activity who have "tuberculous disease." While it is true that most children with the juvenile type of tuberculosis tend to recover without serious extension, it must be remembered that those cases in which the disease spreads and becomes manifestly active, have originated in such masked juvenile infections. This indicates the necessity for early recognition of the juvenile type of tuberculosis and for adopting a regimen which will minimize the danger of its spread. It would seem, therefore, that "tuberculous infection" in children should probably be regarded of sufficiently serious potentialities to warrant somewhat more consideration than it is usually given, even though the actual percentage of children who develop a spread of the disease is small. The management of a child in whom the diagnosis of juvenile tuberculosis has been made will depend upon the evidence of activity indicated by a review of the symptoms and the x-ray changes present. Sometimes a period of observation during which temperature readings were recorded is desirable. Symptomfess Cases.-If there are no symptoms, if normal activity does not produce fatigue, temperature remains below 99.5 0 F., the child is alert with good appetite and gaining normally-in weight, and if a positive skin test with some cal-
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cification in the hilar lymph nodes is the only radiologic evidence of an apparently old or latent infection, then no restriction of his normal activities is necessary. He should be examined from time to time to facilitate the early recognition of any unexpected tuberculous activity, while nutrition should be maintained and regular temperate habits should be encouraged. Subclinical Infection.-A child in whom easy fatigability, even moderate malnutrition with anorexia, occasional slight fever, and any symptom suggesting a subacute infection, are present, should occasion more concern. This is especially true when a positive tuberculin test is accompanied by a chest x-ray in which the hilar nodes are sharply visible, moderately enlarged and have the characteristics previously mentioned as often associated with recent infection and subclinical activity. In such instances, somewhat more careful supervision is indicated. As a rule such children need not be kept from school unless the asthenia is striking, since they are not likely to transmit the infection. Exercise and activity should be restricted to that amount which is well tolerated. Respiratory infection should be prevented insofar as possible by adequate clothing and by guarding against chilling from rain and exposure. Regular habits of eating and sleeping are important and a nutritious, high caloric diet is advisable. Sometimes the appetite may be improved by the administration of vitamin B factors. Morning and evening temperatures should be followed, and the development of fever should indicate rest in bed until it subsides. Regular observation of the clinical status and of pulmonary x-ray changes should be continued on such children until the manifestations of even "subclinical" activity disappear. As the child improves, appropriate relaxation of previous restrictions may be allowed with careful check of their effect on the child's progress. Manifest Tuberculous Disease.-Little need be said regarding the management of children in whom tuberculous disease has become manifest, since the principles of therapy are those now generally employed in all active tuberculosis. These include complete bed rest so long as fever is present; an ade-
TUBERCULOSIS IN CHILDREN
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quate, well balanced, high caloric diet in which all necessary vitamins are included; suitable exposure to fresh air and judicious use of heliotherapy with carefully graduated exposure to sunlight; the prevention of exposure to acute respiratory infections; and such local or symptomatic treatment as may be indicated in the individual child. Continued clinical observation of the patient's response to the infection together with occasional x-ray check on the progress of the lesion should be carried out until the symptoms disappear and the disease is considered in an inactive stage. This may require a number of months. . With the gradual resumptiot:l of normal &.ctivity the same precautions previously suggested in the ~anagement of initial juvenile infections should be observed. As a rule, drugs play little part in the recovery from tuberculosis, and even the newer sulfonamide products have not been shown to have any definite effect. Drug medication should be used only for specific indications. . Tuberculin in Treatment of Phlyctenular Keratoc.onjunctivitis.-Specific therapy with tuberculin has been unsatisfactory and disappointing except in the treatment of one of the more common manifestations of childhood tuberculosisphlyctenular keratoconjunctivitis. Such "desensitization" with tuberculin is apparently the only form of therapy with any constant beneficial effect on this condition. Subcutaneous injections are given once or twice weekly starting with 0.1 cc. of 1: 1,000,000 dilution of Old Tuberculin. The dose is gradually increased, usually by doubling the preceding dose, until 0,5 cc. of 1: 1000 dilution can be given without signs of local reaction. If such local reaction results from any injection, a reduction of the amount given and more cautious increase is indicated. Clinical improvement is slow and even after recovery there is a tendency for recurrence unless the treatment is supplemented by general hygienic and dietary measures for the relief of the underlying infection. ADULT TYPE OF TUBERCULOSIS IN CHILDHOOD
Children who have previously had an initial infection of the juvenile type of tuberculosis may later become infected again
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from contact with an active case. This reinfection produces a pathologic and clinical picture entirely different from the first infection. The allergic sensitivity to tuberculin which develops soon after the initial infection, and which is manifest by the positive tuberculin skin test, involves all the body tissues and changes their reactivity to the tubercle bacilli and its products. Consequently, when some organisms lodge in the lung of an individual sensitized by a previous infection, a· local proliferative reaction in the pulmonary parenchyma develops. This differs from that seen in the spreading infantile type in being slower in developing and in having a greater tendency to be walled off and to remain circumscribed by the connective tissue proliferation. Some of the infecting organisms are carried to the lymph nodes at the root of the lung, but the glandular manifestations are secondary and overshadowed by those of the process in the parenchyma. This lesion as it develops produces local signs of rales and impaired resonance together with constitutional symptoms of fever and asthenia. The clinical and pathologic picture in children with the reinfection type of tuberculosis as well as the treatment is identical with phthisis in adults. It is essentially a disease of later childhood and only occasionally encountered in younger children. It is believed that in some instances such reinfection tuberculosis may result from an autogenous spread from an activated initial lesion rather than from an outside source. The extent of the pulmonary involvement as shown in the x-ray i~ often much greater than anticipated from the physical SIgns. BIB LIOGRAPHY
1. Cooke, ]. V.: Complement Fixation for Tuberculosis in Children. Am.]. Dis. Child., 21: 78, 1921. 2. Sayers, R. R. and Meriwether, 1':. V.: Miliary Lung Disease Due to Unknown Cause. Am. ]. Roentgenol., 27: 337, 1932. 3. Still, G. F.: Common Disorders and Diseases of Childhood. Ed. 5. Oxford University Press, London, 1927, p. 486.